Macromolecular interactions are central to cellular regulation and biological function, and antibody-antigen complexes are often used as a paradigms for molecular recognition. Protein-protein interactions are studied unilizing monoclonal antibodies (mAbs) specific for hen egg white lysozyme, a protein which has long served as a prototpye for investigating the specificity of immune recognition. mAbs HH10, HH26 and HH8 recognize highly coincident epitopes and share over 90% sequence homology, but they differ significantly in their specificity properties. Differences in overall sensitivity of the 3 mAbs to mutations in the antigen epitope reflect differences among them in the relative stabilities of their association and dissociation rates. There are significant correlations between the intramolecular contacts, hydrophobicity, CDR flexibility, kinetics, and specificity of these 3 mAbs. Important structural differences among the 3 mAbs which determine the functional differences involve indirect, long-range effects by noncontact residues. It has been proposed that this type of conformational modulation may play an important role in antibody affinity maturation. A second antibody-antigen model, monoclonal antibodies to the carbohydrate O-antigen of Shigella flexnerii are similar to the anti-HEL mAbs, in that minimal, apparently conservative changes in structure cause significant differences in specificity and affinity properties. This a pattern of emergent properties which is of general significance to molecular recognition and directly applicable to rational design of vaccines and of antibodies with predefined specificity and functional properties.